Staphvlococcus aureus (S. aureus) is Gram-positive, aerobic bacterial pathogen, distinguished from other staphylococcal species by the production of the enzyme coagulase. Sa is a normal inhabitant of the skin and mucous membranes of man and other animals and under certain circumstances invades the body, causing a wide variety of disease conditions ranging from superficial abscesses (boils and furuncles) to disfiguring and life-threatening deep infections such as endocarditis, pneumonia, osteomyelitis, septic arthritis, meningitis, post-operative wound infections, and septicemia. Sa also causes diseases such as toxic shock syndrome.
Like other Gram-positive pathogens, Sa causes disease chiefly through the production and secretion of injurious proteins. These injurious extracellular proteins, or virulence factors (VF), include toxins that damage or dissolve host cells, toxins that interfere with the immune system, and enzymes that degrade tissue components such as proteins, nucleic acids, lipids and polysaccharides.
In laboratory cultures, VF are produced and secreted at the end of the standard exponential growth phase, during a segment of the growth cycle known as the post-exponential phase. The production of VF is coordinately regulated and is thought to represent an attempt by the bacteria to generate new sources of nutrition at a time of rapidly diminishing resources. In the infected individual, this may include an attack on the host defenses that have been mobilized to ward off and contain the infection.
Sa infections are presently treated with antibiotics, which are natural or semisynthetic chemicals that kill or inhibit the growth of bacterial cells. Unfortunately, antibiotics have become less and less effective in treating Sa infections due to the acquired resistance of Sa to these antibiotics. Major nosocomial epidemics are now caused worldwide by strains of Sa that are resistant to most antibiotics. The antibiotic vancomycin is still effective in treating various strains of Sa, although there is a grave danger that those strains will soon acquire resistance to vancomycin from a closely related Gram-positive pathogen, Enterococcus faecalis. 
Since there is little reason to expect the introduction of major new classes of antibiotics, there is an urgent need to develop new methods to control Sa infections, such as interference with the expression of VF. If the bacteria could be disarmed, it is believed that host defenses would do the rest.
In S. aureus, expression of virulence factors is controlled by a global regulator known as agr (Peng, H., et al. J. Bacteriol. 179: 4365-4372 (1988); Regassa, L. B., et al. Infect. Immun. 60: 3381-3383 (1992)). Agr is a genetic locus that contains several genes. Two of these, agrA and agrC, are thought to constitute a signal transduction (STR) pathway that responds to one or more external signalling molecules by activating the transcription of a third gene, agr-rnaIII (Kornblum, J., et al., in Molecular Biology of the Staphylococci, R. P. Novick, ed. (VCH Publishers, New York, 1990); Bourret, R. B., et al. Annu. Rev. Biochem. 60: 401-441 (1991)). The primary transcript of aqr-rnaIII, known as RNAIII, induces transcription of the 20 or more independent genes encoding virulence factors, thereby resulting in the synthesis of VF (Novick, R. P., et al. EMBO Journal 12(10): 3967-3975 (1993)).
It has been shown that laboratory-generated mutant strains of Sa, unable to express VF, exhibit greatly reduced virulence (Foster, et al. Molecular Biology of the Staphylococci, Editor: R. P. Novick, VCH Publishers, New York, pp. 403-420 (1990)). Interference with activation of the agr system would therefore afford a simple means of blocking the expression of VF, and thus interfere with the infective process. Raychoudhury, S. et al. PNAS 90:965-969 (1993) recently described the identification of synthetic chemical compounds that block the expression of alginate, a VF for the cystic fibrosis pathogen, Pseudomonas aeruginosa. It has not been shown, however, whether these chemicals would have any effect on Sa, or offer any potential clinical utility.
The present invention is based upon the discovery of peptides which interfere with the activation of rnaIII transcription and thus prevent expression of VF. Prevention of the expression of VF by S. aureus using peptides which inhibit activation of rnaIII transcription are expected to prevent or treat diseases caused by Staphylococcal infections. Finally, the peptides of the present invention, in addition to treating or preventing diseases or infection caused by S. aureus, also can be used in vitro for preventing colonization of S. aureus.